Study of Octanorm Subcutaneous IG in Patients With PID

Clinical Phase III Study to Evaluate the Pharmacokinetics, Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm 16.5%) In Patients With Primary Immunodeficiency Diseases

This is an open-label phase III study with a 12-week wash-in/wash-out period followed by a 12-month efficacy period. The main goals of the study are to assess the efficacy of octanorm in preventing serious bacterial infections (SBI) compared with historical control data and to evaluate the pharmacokinetic (PK) characteristics of octanorm.

Study Overview

• Status: Completed
• Conditions: Primary Immune Deficiency Disorder
• Intervention / Treatment: Biological: octanorm 16.5%

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Edmonton, Canada, T6G 2V2
    • Octapharma Research Site
  • Montreal, Canada, H3H 1P3
    • Octapharma Research Site
• Czechia
  • Brno, Czechia, 656 91
    • Octapharma Research Site
  • Olomouc, Czechia, 775 20
    • Octapharma Research Site
  • Pilsen, Czechia, 304 60
    • Octapharma Research Site
  • Prague, Czechia, 150 06
    • Octapharma Research Site
• Hungary
  • Budapest, Hungary, 1097
    • Octapharma Research Site
• Poland
  • Bialystok, Poland, 15-274
    • Octapharma Research Site
  • Krakow, Poland, 30-663
    • Octapharma Research Site
  • Krakow, Poland, 31-024
    • Octapharma Research Site
  • Lublin, Poland, 20-093
    • Octapharma Research Site
• Russian Federation
  • Moscow, Russian Federation, 117198
    • Octapharma Research Site
  • Saint Petersburg, Russian Federation, 197101
    • Octapharma Research Site
  • Yekaterinburg, Russian Federation, 620149
    • Octapharma Research Site
• Slovakia
  • Bratislava, Slovakia
    • Octapharma Research Site
  • Košice, Slovakia
    • Octapharma Research Site
  • Martin, Slovakia
    • Octapharma Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Octapharma Research Site
  • California
    • Irvine, California, United States, 92697
      • Octapharma Research Site
    • San Diego, California, United States, 92123
      • Octapharma Research Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Octapharma Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68046
      • Octapharma Research Site
  • Ohio
    • Toledo, Ohio, United States, 43617
      • Octapharma Research Site
  • Texas
    • Frisco, Texas, United States, 75034
      • Octapharma Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age of at least 2 years up to and including 75 years.
2. Confirmed diagnosis of PI as defined by the ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded.
3. Patients with at least 6 infusions on regular treatment with any IVIG, there of a minimum of the last 2 months on the same product prior to entering the study. Constant IVIG dose between 200 and 800 mg/kg body weight (±20% of the mean dose for the last 6 infusions).
4. Availability of the IgG trough levels of 2 previous IVIG infusions before enrollment, and maintenance of greater than or equal to 5.0 g/L in the trough levels of these 2 previous infusions.
5. Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study.
6. For adult patients: freely given written informed consent. For minor patients: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with the applicable regulatory requirements.
7. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study.

Exclusion Criteria:

1. Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period.
2. Known history of adverse reactions to IgA in other products.
3. Patients with body mass index ≥40 kg/m2.
4. Exposure to blood or any blood product or plasma derivatives, other than IVIG treatment for PID, within the past 3 months prior to the first infusion of octanorm.
5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as Polysorbate 80).
6. Requirement of any routine premedication for IgG administration.
7. History of malignancies of lymphoid cells and immunodeficiency with lymphoma.
8. Severe liver function impairment (ALAT 3 times above upper limit of normal).
9. Known protein-losing enteropathies or proteinuria.
10. Presence of renal function impairment (creatinine greater than 120 uM/L), or creatinine greater than 1.35 mg/dL), or predisposition for acute renal failure (e.g., any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs).
11. Treatment with oral or parenteral steroids for greater than or equal to 30 days or when given intermittently or as bolus at daily doses greater than or equal to 0.15 mg/kg.
12. Treatment with immunosuppressive or immunomodulatory drugs.
13. Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm.
14. Treatment with any investigational medicinal product within 3 months prior to first infusion of octanorm.
15. Presence of any condition, that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial.
16. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm.
17. Known or suspected HIV, HCV, or HBV infection.
18. Pregnant or nursing women.
19. Planned pregnancy during the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Octanorm 16.5%; octanorm 16.5%, human normal immunoglobulin for subcutaneous (SC) administration.	Biological: octanorm 16.5%; octanorm 16.5%, human normal immunoglobulin for subcutaneous (SC) administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of SBI Per Person-year	The primary efficacy outcome is the rate of SBI (Serious bacterial infections - defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment.	Every 4 weeks until the final evaluation at week 65.
AUC(t) at Steady-State Conditions	The primary endpoint with respect to the PK investigations is the area under the curve AUC(t) (i.e., AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardised to 1 week) at PKSC2 at steady-state conditions.	Measured at Week 28 before the start of the SC infusion, 10 minutes before the end of the infusion, and at 2 h, 1, 2, 3, 4 and 7 days after the end of the infusion. Calculated and averaged.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Annual Rate of All Infections of Any Kind or Seriousness.	The annual rate of all infections of any kind or seriousness.	Up to 65 weeks
Non-serious Infections	Non-serious infections (total and by category).	Up to 65 weeks
Cmax of Total IgG and IgG Subclasses	Cmax (Maximum Plasma Concentration) of total IgG and IgG Subclasses, where the mean value was calculated and reported	Measured at week 28
Tmax of Total IgG and IgG Subclasses	Tmax (Time to Maximum Plasma Concentration) of total IgG and IgG Subclasses	Measured at Week 28 for all patients, median value was calculated
AUC of Total IgG and IgG Subclasses	AUC (Area Under the Concentration-Time Curve) of total IgG and IgG Subclasses calculated for all patients and mean value was calculated and reported	Measured at Week 28
Trough Levels of Serum IgG	Trough levels of serum IgG, IgG1, IgG2, IgG3, IgG4 at PK 7 days after 28th infusion of octanorm measured for all patients and median value was calculated and reported	Measured once at Week 28, seven days after 28th infusion of octanorm
IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ])	IVIG to Octanorm Dose Conversion Factor (based on the area under the concentration-time curve [AUCτ]) -- determined by least-squares regression Model which was without restriction of the intercept.	AUC Measured at Week 28

Collaborators and Investigators

• Sponsor: Octapharma

Publications and helpful links

General Publications

• Kobayashi RH, Gupta S, Melamed I, Mandujano JF, Kobayashi AL, Ritchie B, Geng B, Atkinson TP, Rehman S, Turpel-Kantor E, Litzman J. Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (Octanorm [Cutaquig(R)]) in the Treatment of Patients With Primary Immunodeficiencies. Front Immunol. 2019 Feb 4;10:40. doi: 10.3389/fimmu.2019.00040. eCollection 2019. Erratum In: Front Immunol. 2022 Dec 20;13:1110388.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): June 9, 2020
• Study Completion (ACTUAL): June 9, 2020

Study Registration Dates

• First Submitted: June 21, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (ESTIMATE): June 27, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 17, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: PID
• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
• Other Study ID Numbers: SCGAM-01